PROJECT SUMMARY/ABSTRACT Polypharmacy (PP), or the concurrent use of multiple medications, affects up to 92% of older adults with cancer. It has been associated with adverse outcomes in these patients including poor adherence to and tolerance of cancer therapy, decrease in physical functioning, unplanned hospitalizations, falls, increased symptoms, and lower survival. ?Deprescribing,? or the planned discontinuation of medications which may be potentially unsafe or inappropriate, is an intervention strategy which has the potential to decrease PP and improve outcomes. Deprescribing has not been studied in older adults with cancer receiving chemotherapy. Given the association of PP with reduced relative dose intensity (RDI) of chemotherapy, a ratio of dosing received to standard dosing, a deprescribing intervention could improve RDI in older adults with cancer receiving curative-intent chemotherapy; RDI of chemotherapy is a predictor of survival in these patients. This proposal presents a five-year research and career development plan focused on investigating both the preliminary efficacy and the optimal implementation of deprescribing interventions in older adults with PP and curable cancers. The candidate, Dr. Erika Ramsdale, is an Assistant Professor of Medicine at the University of Rochester and is board-certified in both Oncology and Geriatric Medicine. This proposal builds upon her prior work demonstrating that PP is prevalent in older adults receiving chemotherapy and that a pharmacist-led deprescribing intervention is feasible to implement in an oncology clinic with high patient satisfaction. The aims of the proposed study are: 1/adapt and refine potentially scalable deprescribing interventions; 2/investigate the effects of deprescribing interventions on RDI and other adverse outcomes in older adults undergoing curative- intent chemotherapy, and 3/identify barriers and facilitators of deprescribing interventions for patients, oncologists, and pharmacists. Focus groups and interviews with pharmacists, oncologists, nurses, primary care providers, and patient advocates will allow initial adaptation of the proposed interventions. A ?pre-pilot? cohort of 8 patients with PP and cancer planned to receive curative-intent chemotherapy will undergo a pharmacist-led deprescribing intervention with additional iterative adaptations. Then, 72 patients will be allocated to a pharmacist-led deprescribing intervention versus patient education intervention in a cluster- randomized trial of 12 oncologist clusters. The proposal describes a comprehensive mentorship and training plan to develop complementary skills in clinical trial design, implementation science, and data science (encompassing informatics and statistics). Under the guidance of her primary mentor Dr. Supriya Mohile, co- mentors Dr. Gary Morrow, Dr. Lisa Zubkoff, and Dr. Holly Holmes, and advisors Dr. Sally Norton and Dr. Martin Zand, she will advance her skills in these areas with the long-term goal of becoming an independent cancer care delivery researcher implementing and testing multi-level interventions, including technology interventions, to address polypharmacy in older adults with cancer.